Naturally occurring non-nutritive agents present in plants such as flavonoids, phenolic compounds, glucosinulates, terpenes and many others are believed to have disease preventive properties. Diets containing some of these substances have been shown to be protective against diseases such as colon and breast cancer in animals (Kuo, S. M. 1997. Clin. Rev. Oncogenesis 8:47–69; Verhoeven et al. 1996. Cancer Epid. Biomark. Prev. 5:733–748; Bradlow et al. 1991. Carcinogenesis 12:1571–1574; Lamartiniere et al. 1995. Proc. Soc. Exp. Biol. Med. 208:120–123). The clinical relevance of such natural phytochemicals is dependent on extrapolation from epidemiological data and from experiments in animal models of diseases of interest.
Purified flavenoid compounds isolated from citrus juice have been tested individually for their effects on carcinogenesis, tumor cell growth and invasion of tumor cells into normal cells (Attaway, J. A. 1994. In: Food Phytochemicals for Cancer Prevention, ACS Symposia Series #546, Huang et al. Eds., pp. 240–248) In particular the polymethyoxylated flavenoids, tangeretin and nobeletin, were shown to have anti-carcinogenic activity.
Extracts of bitter-orange peel are used as an herbal drug (Bisset, N. G. 1994. Herbal Drugs and Phytopharmaceuticals, CRC Press: Boca Raton). Conditions treated include loss of appetite and dyspeptic complaints. The main components of the extract include limonene and flavonoids such as neohesperidin and naringin.
Several patents disclose the use of various phytochemicals in combination with orange peel extract or dried orange peel. CN 1200277 describes use of a composition composed of 16 plant components, one of which is dried orange peel, for treatment of psychosis and nervous system disease. CN 1116945 describes the use of orange peel along with several other natural products in a capsule form to sooth the liver, nourish the stomach, remove stasis, stop pain and cure various gastric diseases. CN 1111134 discloses an oral liquid containing orange peel, among other things, for treatment of neurastenia, chronic bronchitis, asthma, coronary heart disease, high blood lipid levels, hepatitis, cytopenia, senility and immune dysfunction. CN 1106673 is a patent for a disease-preventing nutrient tea that is produced from a variety of products, including soaked, crushed orange peel. CN 1077124 describes a Chinese herb preparation for treatment of iron-deficiency anemia that is composed of a number of ingredients, including dried orange peel. Finally, a Japanese patent (JP 57156761) discloses a heat-generating pad for orthopedic diseases that contains extracts and powders of many plants, including orange peel.
It has now been found that an extract of orange peel has biological activity as a treatment and preventative agent for cancer.